title: Diabetes-induced morphological, biomechanical, and compositional changes in ocular basement membranes.
abstract: The current study investigates the structural and compositional changes of ocular basement membranes (BMs) during long-term diabetes. By comparing retinal vascular BMs and the inner limiting membrane (ILM) from diabetic and non-diabetic human eyes by light and transmission electron microscopy (TEM), a massive, diabetes-related increase in the thickness of these BMs was detected. The increase in ILM thickness was confirmed by atomic force microscopy (AFM) on native ILM flat-mount preparations. AFM also detected a diabetes-induced increase in ILM stiffness. The changes in BM morphology and biophysical properties were accompanied by partial changes in the biochemical composition as shown by immunocytochemistry and western blots: agrin, fibronectin and tenascin underwent relative increases in concentration in diabetic BMs as compared to non-diabetic BMs. Fibronectin and tenascin were particularly high in the BMs of outlining microvascular aneurisms. The present data showed that retinal vascular BMs and the ILM undergo morphological, biomechanical and compositional changes during long-term diabetes. The increase in BM thickness not only resulted from an up-regulation of the standard BM proteins, but also from the expression of diabetes-specific extracellular matrix proteins that are not normally found in retinal BMs.
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, United States.
authors.forename: Margaret
authors.initials: M
authors.lastname: To
authors.forename: Alexandra
authors.initials: A
authors.lastname: Goz
authors.forename: Leon
authors.initials: L
authors.lastname: Camenzind
authors.forename: Philipp
authors.initials: P
authors.lastname: Oertle
authors.forename: Joseph
authors.initials: J
authors.lastname: Candiello
authors.forename: Mara
authors.initials: M
authors.lastname: Sullivan
authors.forename: Paul Bernhard
authors.initials: PB
authors.lastname: Henrich
authors.forename: Marko
authors.initials: M
authors.lastname: Loparic
authors.forename: Farhad
authors.initials: F
authors.lastname: Safi
authors.forename: Andrew
authors.initials: A
authors.lastname: Eller
authors.forename: Willi
authors.initials: W
authors.lastname: Halfter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001485:Basement Membrane / Q000737:chemistry* / Q000648:ultrastructure; D015153:Blotting, Western; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004548:Elasticity; D016326:Extracellular Matrix Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D012160:Retina / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D016326:Extracellular Matrix Proteins
keywords: basement membrane; collagen IV; inner limiting membrane; laminin; proteoglycans